An automated analyzer for clinical examination dispenses certain amounts of a sample and a reagent to stir and react the sample and the reagent. The automated analyzer measures absorbance of a reaction solution throughout a certain time and calculates a concentration, an activity value, and the like of a measurement target substance based on a measurement result.
Reagents for each analysis item, a standard solution for calibrating the reagents, an quality control sample that is measured to check the states of the analyzer and the reagents in the analysis, and the like are necessary in addition to the analyzer in the analysis for clinical examination. The materials other than the analyzer are combined to obtain ultimate analysis performance.
Examples of factors inside the analyzer that directly affect the analysis performance include a sampling mechanism, a reagent dispensing mechanism, a stirring mechanism, an optical system, a reaction container, and a thermostatic bath. Examples of factors other than the automated analyzer, include acidity or alkalinity of a reagent, a sample, and a control specimen.
To use the automated analyzer on a daily basis, the factors need to be checked to determine whether the clinical examination can be normally performed. The factors are checked, for example, as follows.
(1) Calibration Using Standard Solution Calibration is carried out for each reagent bottle of each item. A blank solution and a standard solution are measured, an origin is determined, an absorbance per unit concentration is calculated, and a conversion factor (hereinafter, abbreviated as “K-factor”), is calculated. In general, the clinical technologist checks the magnitude of the absorbance and a chronological change in the K-factor to determine the quality of the calibration result.
(2) Quality Control
A quality control sample with a known concentration is measured after the calibration to check the difference from a reference value. In the measurement of a patient specimen, the quality control sample is periodically measured every certain time to check the difference from a tolerance. If the tolerance is exceeded, it is determined that there is a problem in one of the reagent and the analyzer, and inspection is performed.
The absorbance is measured for a plurality of times during the reaction of the sample and the reagent, and the absorbance is recorded as time-series data. The time-series data is also called reaction process data. The data in daily examinations are checked based on the reaction process data. The method varies depending on the analysis method. The measurement method of clinical examination can be classified into two types, a rate method and an endpoint method, depending on the analysis method.
The rate method is mainly used to measure the activity of enzyme components included in the sample, and an activity value of the enzyme, not the concentration of the enzyme, is measured. In the measurement method, a certain amount of substrate is added as the reagent. The enzyme consumes the substrate, and a changed element is measured. If the concentration of the substrate is high to some extent, the enzyme reaction speed approaches a theoretical upper limit. The reagent of biochemical item measurement includes enough substrate. Therefore, if the sample and the reagent normally react, the measurement value of the reaction usually linearly changes by certain amounts relative to the time change.
Conventional detection methods of data abnormality during measurement in the rate method include linearity check and ABS limit. In the linearity check, the linearity of the absorbance change is checked for an analysis item of the rate method. A difference between amounts of absorbance change in the first half and the second half in a certain photometry period is obtained, and it is determined that the change does not indicate linearity if the difference is beyond a designated linearity check value. If the concentration or the enzyme activity value of the measured sample is abnormally high and is beyond the measurable range of the reagent, the substrate or the coenzyme in the reagent is all consumed before the end of photometry period. In such cases, the absorbance value rapidly changes, and a correct measurement value cannot be obtained. Therefore, a reaction absorbance limit value (ABS limit) for the upper limit or lower limit of the absorbance is set to detect the abnormality of the data.
The concentration of components, such as protein and fat, included in the sample are mainly measured by the endpoint method. Since the substance generated by the reaction of the components in the sample and the reagent approaches a certain amount with time, the measurement value also approaches the certain value with time.
An example of a conventional detection method of data abnormality during the measurement in the endpoint method includes prozone check. In a reagent using turbidimetric immunoassay, such as IgA (immunoglobulin A) and CRP (C reactive protein), protein may be deposited as a sediment due to the influence of salt concentration of the reagent composition. The sediment may fluctuate the reaction process data, and the fluctuation actually occurs at the second half section of the reaction time in many cases. If the fluctuation occurs in photometry time points used for the concentration calculation, the concentration value cannot be accurately obtained. Examples of the method for checking the fluctuation include an antibody re-addition method and a ratio of reaction rate method, which are methods of issuing an alarm when a designated limit value is exceeded in a parameter.
Examples of methods of using the reaction process data to determine the presence or absence of abnormality include known methods disclosed in Patent Literatures 1 and 2. In the method of Patent Literature 1, a chemical reaction model is used in advance, reference time-series data is generated and stored, reaction process data of a sample is compared with the reference time-series data, and it is determined that there is an abnormality if the deviation is large. In the method of Patent Literature 2, an absorbance change is approximated by a function stored in advance, and the abnormality is determined from the magnitude of the deviation between the absorbance change calculated by an approximated function and the actually measured absorbance.